Researchers enjoying a
pharmaceutical industry bounty because of their willingness to engage in applied research
to increase the effectiveness of existing drugs, sometimes find themselves legally
cornered because of the "confidentiality agreements"
they have signed.

A 1998 case at
the Toronto Hospital for Sick Children involved the trial of a modified form of a drug
(Deferiprone) which promised the advantage that it could be given orally, rather than
intravenously. Having published the results of a preliminary study in the New England Journal of Medicine, it was
then found that certain patients
showed signs of toxic liver damage. Rather than give up and allow the funds to be diverted
to other avenues, it was proposed to try to find ways of predicting which patients would
benefit, and which would respond adversely.

To discriminate
between the two groups of patients required that administration of the drug be continued,
rather than stopped. Accordingly the researcher approached the sponsoring pharmaceutical
company seeking permission to change the consent form which experimental subjects were
required to sign in order to inform them of the new risk. The pharmaceutical company
(Apotex: research director, Michael Spino) refused, and threatened the investigator with
legal action if she divulged her findings to her patients.

After bathing in the
glory of having a paper by one of its researchers published in the prestigious New England Journal of Medicine, the
Hospital now refused to back the researcher, and pressed her to resign. A usual tactic in
such cases is to brand the alleged offenders as persistent "trouble
makers", or to dismiss the matter as a "personality
conflict" between people with big scientific egos. The Hospital's President,
Michael Strofolino, characterized the dispute as what Globe
& Mail Editor Margaret Wente describes as "a spat propelled by a small group of troublemaking malcontents".
She further observed that evidently Strofolino "had sold this
version of events to the trustees, who, when last heard from, declared it none of their
business."

With the support of
some colleagues (Brenda Gallie, Helen Chan, John Dick, Peter Durie), the researcher "went public", and pressure mounted for a full enquiry. One
commentator noted in a letter to to Toronto Globe &
Mail:

In failing ...[her] when she
needed them most, it is now clear that some members of the University's Faculty of
Medicine heard her muffled cries of academic freedom from the back room, yet their
response was to serve another round of drinks and turn the music up louder. With the
bombshell relevations in the ...affair, the plug may have been pulled on this
business-sponsored party, and hopefully a sober re-examination of the University's
neglected role and responsibility toward independent inquiry and academic freedom can
begin.

The
modern research system being structured to promote competition rather than collaboration,
it is noteworthy that Nancy Olivieri had supportive colleagues. Such colleagues depend on
the institution for advancing their careers (research space, funds, etc.). At an
individual level there is more to gain by backing one's Administration rather than one's
colleague.

Thus, the
decision to support a colleague is not lightly made. There may be days and weeks of
soul-searching, dealing with worries about getting another appointment if there are
dismissals, worries about the hum-drum details of life such as where the next mortgage
payment and school bill will come from if justice does not prevail.

Thus, not
surprisingly, many colleagues were not supportive. Prominent among these was professor and
head of the hospital's division of clinical pharmacology, Dr. Gideon Koren, a recent
recipient of the first Canadian chair in child health research, the result of a $2-million
gift from the Canadian Imperial Bank of Commerce to the hospital. Another was Dr. Sergio
Grinstein, holder of the University of Toronto Pitblado Chair in Cell Biology and, until
recently, a member of the Gairdner Foundation Committee which adjudicates Canada's
equivalent of Nobel Prizes.

Koren
went into action at the early "soul searching"
stage to undermine the support which Olivieri so needed.

Usually,
in such cases, a little light lobbying in corridors, well out of ear-shot of others, is
sufficient to shepherd the waverers back to the fold. But, being MDs with the possibility
of clinical practice to fall back on financially, some of Olivieri's colleagues were not
so vulnerable. So Koren had to institute an anonymous "poison
pen" letter writing compaign. It was not until late 1999, following the hiring
of a private detective and the testing of DNA attached to postage-stamps, that Koren was
identified as author of at least four such letters. Reporters Krista Foss and Andrew
Mitrovica of The Globe and Mail
(Tuesday, December 21, 1999) described this as: "not a mystery
novel, but instead the latest skullduggery at
Toronto's Hospital for Sick Children".

In the letters,
supportive colleagues were referred to as "unethical"
and "a group of pigs", and at least one was advised
to leave the hospital. One letter was sent to as many as 40 people in the hospital,
according to Dr. Durie, who was told that he should leave the institution, and that he was
a British version of a "foul air balloon."

"How did you ever get yourself in the middle of this group of pigs? Or did
you think that their shit won't touch you?," the same letter asked. A final
letter, received by Dr. Durie says he is "contaminating our air
and fabric" and then refers to his candidacy for a job at another hospital.

This final
revelation gave the story sufficient momentum to propel it beyond Canadian media, ... to 60 Minutes and The
New York Times.

Dr. Durie
informed several people at the hospital about the letters he was receiving, including the
President. He asked for an investigation of the individual he suspected was sending them,
but the Hospital declined. Accordingly, Olivieri's colleagues had to spend around $300,000
to get the overwhelming evidence, leading to Koren's confession.

DNA
evidence was also used to catch Grinstein, according to reporter Karen Birmingham in the
May 2000 issue of Nature Medicine (6,
485). A Canadian expert on drug development and drug regulatory law, Dr. Michele
Brill-Edwards, who had worked at the Bureau of Human Prescription Drugs at the Health
Protection Branch, Ottawa, wrote an article in September 1998 for the Toronto Globe & Mail "calling for the Hospital for Sick Children administration to admit its
failings and resign." This provoked a personal signed letter from
Grinstein in October 1998, which said that Brill-Edwards has "...cast
a shadow over the hospital...", and urged her to redress "...the damage you may have done to the Hospital
and its community of scientists and administrators."

Brill-Edwards
received an anonymous note in July 1999 shortly after she had attended a regulatory
meeting on the safety and efficacy of Deferiprone. The note read:

"Deferiprone
has been approved by the FDA.

Dr. Olivieri has left the Hospital for Sick Children.

HSC has just completed its most
successful fund raising campaign ever.

Dr. B. Gallie is leaving HSC.

The Board of Trustees, the
heads of Research, Pediatrics and the CEO of HSC remain in charge of the institution.

All's well that ends well
(demagogues and professional agitators notwithstanding!)."

The note was wrong on two counts. Deferiprone had not received FDA approval, and Olivieri
had not left the HSC. Brill-Edwards found the note "intimidating"
and having had Grinstein's DNA identified and obtained his confession, reported the matter
to David Naylor, the Dean of the Faculty of Medicine at the University of Toronto.

In an article
entitled "Medicine, Morals and Money"
Margaret Wente described the failure of correct administration action as resulting from
"a fundamental misreading of the issue as a mere
contractual and scientific dispute (Globe
& Mail. Thursday, December 23, 1999). It was also noted that,
since 1998 Olivieri has been "demoted, then restored, then
harassed. She has been smeared with allegations attacking her competence, integrity,
sanity and personality, ...".

Meanwhile, the
Head of Apotex, Barry Sherman, was raising the stakes with some sweet philanthropic
offerings ($20 million) to the University of Toronto, which is affiliated with the
Hospital for Sick Children. In return, then University President, Robert Pritchard, lobbied the
Government to extend the period of review of drug patent protection regulations.

The
drug in question in the Olivieri affair was to be Apotex's first patented, non-generic
drug, and it was potentially worth hundreds of millions (see Krista Foss & Nicola
Luksic, Globe & Mail. September
16th 1999). When interviewed by Correspondent Leslie Stahl in 60
Minutes, Sherman referred to Olivieri as "nuts".
When asked to delete the remark, Stahl replied: "Yeah, but you
know, we're reporters. We're not your pals." (See also Krista Foss.
Globe & Mail. 22nd December
1999).

However, some
reporters still seem unaware of the depth of the problem. Margaret Wente in "Medicine, Morals and Money" (see above), referring to
the Olivieri affair as "Canada's worst academic and
research scandal in decades", gives the impression that otherwise all
is well. Although, information in the area is difficult to obtain, it is the impression of
the author of this web-page on the failings of the peer review system that the Olivieri
scandal may be far from "Canada's worst". It may be
the tip of a much more ominous iceberg, as hinted at by John LeCarre in the
epilogue of The Constant Gardner. It is receiving public attention,

because it involves research with an immediate clinical
impact on child health,

because the person under attack is female and attractive,

because her supportive colleagues have sufficient
financial independence to engage in professional risk-taking, and

because her attackers have not covered their tracks too
well.

Whatever else one might say, Gideon
Koren and Sergio Grinstein displayed remarkably bad judgement. Yet, they had been for many
years, and probably still are,
major participants in the peer review process in Canada and elsewhere. In
2001 Grinstein was still on the Editorial Board of the Journal
of Experimental Medicine.

A further article by Karen Birmingham
(2000. Nature Medicine6,
609-610) summarized the 9 page Report
of a panel investigating Gideon Koren, which was signed for the University of Toronto by
the President, Robert Prichard, and for the Hospital for Sick Children by its CEO, Michael
Strofolino:

"Being
an accomplished medical researcher and teacher is sufficient to excuse behavior that
includes destroying institutional equipment, harassing colleagues and lying to them and to
superiors - at least at the University of Toronto and at the Hospital for Sick Children in
Toronto."

The President of the University of
Toronto Faculty Association commented:

"The decision fails to ensure a harassment-free environment that is critical to
scientific work... and that the Hospital and the University have damaged themselves by
their failure to protect academic freedom and prevent harassment of scholars."

Sergio Grinstein may have
faired even better. The Hospital investigated his conduct as "an
internal matter." A spokesperson says "the Hospital
has investigated Grinstein's conduct and taken the appropriate action."

Although the
possible penalties have been mitigated by "Koren's hitherto unblemished career record," the Report notes that "specific allegations of
alleged research misconduct remain outstanding" and have been referred to the
Dean of the Faculty of Medicine. There is also an "open verdict"
on allegations that Koren submitted false evidence. The case is still open also on the
possibility that certain letters, dated 18th December 1996 and 8th February 1997, were
actually prepared at a later date to buttress Koren's submission to the Naimark inquiry
(see below) and to discredit Olivieri.

When asked by
the reporter for her opinion, Olivieri pointed to defects in the study. This prompted an
attack by Dr. S. Macleod (McMaster University)on Dr. Olivieri's integrity (28th November;
letter to Globe & Mail).

Dr.
Brill-Edwards promptly replied: "Dr. Sweeney touted the study
as vindicating the drug. The Globe, doing its job, sought and received Dr. Olivieri's response. In meeting
her public obligation to respond, Dr. Olivieri pointed to a potential fatal flaw in the
claimed victory. The study results that purport vindication account for only a small
fraction of the patients studied."

Olivieri was not unscathed materially. In June 2001 Nature Medicine (7,
644) reported that "Olivieri's lab was closed down in
1998 and the administration has not provided her with new space."
The University of Toronto Faculty Association President noted in an open
letter that: "UTFA alleges that the University
failed utterly in its duty to act to protect Dr. Olivieri, her academic
freedom, the academic freedom of all of us and the fundamental rights of
the public which we in the University have the duty to uphold."

However, Nature Medicine reports
that: "the Hospital for Sick Children ... has
refused to allow the grievance panel to access relevant documents."
Happily, "Olivieri was selected ... as a recipient of the 2001 award
by the Civil Justice Foundation in Washington," which noted:

"The
legal assaults which you have endured in your battle against the
drug company, and in your battle against the medical establishment
appear to have been fought with the type of uncommon bravery that
is rarely seen. It is for this reason that our trustees have
unanimously chosen to recognize you for this most prestigious
award."

For more on this, please go to the web-site of the University of British Columbia's Centre
for Health Services and Policy Research and download Tales
from the Other Drug Wars(Click Here),
which includes a fine article by Michele Brill-Edwards entitled "Canada's
Health Protection Branch: Whose Health, What Protection?"

Or, on a lighter note, read John Le
Carré's novel The Constant Gardner.
The author's note at the end states:

"As my journey through the pharmaceutical jungle
progressed, I came to realize that, by comparison with reality, my
story was as tame as a holiday postcard. ... I drew on several cases,
particularly in the North American continent, where highly qualified
medical researchers have dared to disagree with their pharmaceutical
paymasters and suffered vilification and persecution for their
pains."

On June 4th 2003, Gay Abbate
reported in the Toronto Globe and Mail
that:

"Dr. Gideon Koren ... has been
ordered to appear before the College of Physicians and Surgeons of
Ontario for an official reprimand for writing poison-pen letters to
supporters of Dr. Nancy Olivieri."

This
page is concerned with the funding of activities by third parties and the ways
they go about evaluating requests for such funding.

In the light of the events of 11th September 2001 we can accordingly note that
there are three groups of potential supporters of organizations such as those of
Bin Laden. (i) Those who will support whatever the circumstance. (ii) Those who
will never support. (iii) Those who vacillate between these extremes. Will the
willingness of the latter group to provide support be encouraged or diminished
by events such as are described on this "scullduggery" web-page?